On 30 October, the US Food and Drug Administration’s (FDA) advisory committee (AdCom) voted in favour of withdrawing AMAG’s injectable therapy Makena (hydroxyprogesterone caproate) from the market following the failed Prolong study.
The Prolong trial was conducted following Makena’s approval, as a post-approval confirmatory study. Nine committee members voted for Makena’s withdrawal and seven to keep the drug on the market with a requirement of a new trial to confirm the drug’s efficacy.
On the heels of the news, AMAG’s stock dropped more than 25%. Makena, a progestin indicated to reduce the risk of preterm birth in pregnant women with a history of spontaneous preterm birth, received accelerated approval in 2011.
GlobalData believes that either an FDA decision to remove the drug from the market or a request for a new confirmatory trial will have significant implications for patients and the company.
With Makena being the only FDA-approved drug for the indication, patients will be left with minimal treatment options. Some AdCom committee members expressed concerns that a lack of an FDA-approved drug on the market could result in patients increasing their use of generic forms of hydroxyprogesterone caproate (the active ingredient in Makena) made by compounding pharmacies, which in the past have caused physicians concern as they have been associated with safety issues.
On the other hand, the scenario of a new confirmatory study while Makena remains on the market comes with its own set of issues. Notably, the Prolong study took nine years to complete. Following Makena’s FDA approval, some physicians see the enrolment of patients in a placebo-controlled trial – when an efficacious treatment option exists – as unethical. Thus, a similar situation would likely arise that would preclude the company from running an adequately designed trial, acceptable to the FDA.